Comparative examination of subcutaneous tissue reaction to high molecular materials in medical use

Tomida M, Nakano K, Matsuura S, Kawakami, Kawakami T

Description

Polypropylene (PP), Polyethylene (PE) and polytetra-fluoroethylene (FE) are high molecular materials in medical use. They are also used as the negative control materials for ISO 10993-6 international standard biological evaluation of medical devices. We examined tissue reactions to these materials embedded subcutaneously in the dorsal area of male ddY mice. One week and 12 weeks after embedding, the tissue surrounding the embeddingg site was removed and then histopathological examination was performed. Our results demonstrate that the basic histopathological reaction is the formation of fibrous capsule consisting of granulation tissue around the embedded materials. Based on our results, we believe that the high molecular materials such as, PP, PE and FE, can be considered for medical use as a biomaterials within the body.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 11
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

2) Kawakami T_Umbruchvorlage 03.06.11 17:13 Seite 249
June 21, 2011 Eu Ro PEa n Jo u R n a l o f MEd IC a l RE SEa RCH 249
Eur J Med Res (2011) 16: 249-252 © I. Holzapfel Publishers 2011
Co MPa Ra t Iv E Ex a MIn a t Io n o f Su b Cu t a n Eo u S t ISSu E REa Ct Io n t o
HIg H Mo l ECu l a R Ma t ERIa l S In MEd ICa l u SE
1 2 3 2M. t omida , K. n akano , S. Matsuura , t . Kawakami
1d epartment of o ral Physiology, Matsumoto d ental u niversity School of d entistry, Shiojiri, Japan
2Hard t issue Pathology u nit, Matsumoto d ental u niversity Institute for o ral Science, Shiojiri, Japan
3d epartment of b iology, Matsumoto d ental u niversity School of d entistry, Shiojiri, Japan
Abstract PE, 0.79mm; and f E, 0.94mm. t he materials were
Polypropylene (PP), Polyethylene (PE) and polytetra- then disinfected by autoclave treatment.
fluoroethylene (f E) are high molecular materials in
medical use. t hey are also used as the negative control a n IMa l S
materials for ISo 10993-6 international standard
biological evaluation of medical devices. We examined tis- a total of 18 male 9-week-old ddY mice weighing
sue reactions to these materials embedded subcuta- about 35g (30-40g) each were purchased from Japan
neously in the dorsal area of male ddY mice. o ne Sl C Inc. (Hamamatsu, Japan). t he animals were kept
week and 12 weeks after embedding, the tissue sur- in plastic cages with a floor mat (Paper Clean: Peparlet
rounding the embedding site was removed and then Co., l td., Shizuoka, Japan) under controlled
air-condihistopathological examination was performed. o ur re- tioned room with water and solid diet (Picolab Rodent
sults demonstrate that the basic histopathological reac- d iet 20: Japan Sl C Inc., Hamamatsu, Japan) during
tion is the formation of fibrous capsule consisting of the experimental periods.
granulation tissue around the embedded materials. t he Matsumoto d ental u niversity Committee for
based on our results, we believe that the high molecu- a nimal Experimentation approved the study.
lar materials such as, PP, PE and f E, can be
considered for medical use as a biomaterials within the body. MEt Ho d S
Key words: t issue reaction; Histopathological evalua- Prior to the examination, inhalation anesthesia was
tion; High molecular material used with isoflurane (Isoflu: d ainippon Sumitomo
Pharma Co., o saka, Japan) and gas-air mixture (4.0%
In t Ro d u Ct Io n concentration). Immediately after the dorsal areas of
the mice were disinfected with 70% ethanol, the
incibecause high molecular polymer is used as a material sions were made, and the materials were injected
subin vivo, it should be evaluated for safety according to cutaneously into the connective tissues. t he skin
surISo standard 10993-6 [1, 2]. Polypropylene (PP), Poly- face at the incision sites was sutured using suture
ethylene (PE) and polytetrafluoroethylene (f E) are string. t he site was marked every 2 weeks until the
fihigh molecular materials in medical use, although the nal examination period at 12 weeks.
tissue reaction in a single material is not examined. a t 1 week and 12 weeks after the injection, 3 mice
t hey are also used as the negative control materials from each group were anaesthetized with isoflurane
for ISo 10993-6 international standard biological eval- and gas-air mixture, and the tissues surrounding the
uation of medical devices. In the present investigation, injection sites were excised. t he excised tissues were
we examine the local effects after implantation of the immediately fixed in 4% paraformaldehyde/0.5M
above-mentioned materials. t he data led us to believe phosphate buffered solution, embedded in paraffin,
that many researchers can know the tissue reactions to and sections prepared.
these biomaterials itself. t his means next step of de- t he tissue sections were stained with hematoxylin
veloping new biomaterials. and eosin and examined by light microscopy for
histopathological changes. We followed the
InternaMa t ERIa l S a n d MEt Ho d S tional o rganization for Standardization (ISo )
guidelines for evaluating the local effects of injection mate-Ma t ERIa l S
rials [2].
t he materials to be examined include 1)
Polypropylene (PP: Prime Polypro; Prime Polymer Co., l td., RESu l t S
t okyo), 2) Polyethylene (PE: HI-ZEx , Prime Polymer Po l YPRo PYl En E: PP
Co., l td., t okyo) and 3) Polytetrafluoroethylene (f E:
t eflonRt f E; d u Pont-Mitsui f luorochemicals Co., Histopathological examination of the Polypropylene
l td., t okyo), in discoids 6mm in diameter. Materials group, 1-week-specimens, showed granulation tissue
were prepared in the following thickness: PP, 0.54mm; proliferation around the embedded material (f ig. 1,2) Kawakami T_Umbruchvorlage 03.06.11 17:13 Seite 250
250 Eu Ro PEa n Jo u Rn a l o f MEd ICa l RESEa RCH June 21, 2011
Fig. 1. PP-1: g ranulation tissue formation surrounding the material PP. (PP, 1-wk-specimen, x100); PP-12: g ranulation tissue
with some necrotic tissue foci and inflammatory cell infiltration. (PP, 12-wk-specimen, x100); PE-1: Proliferation of scattered
granulation tissue around the embedded material PE. (PE, 1-wk-specimen, x100); PE-12: t he granulation tissue changed to
fibrous tissue. (PE, 12-wk-specime, x100); f E-1: t hin layered fibrous capsule tissue around the material f E. (f E, 1-wk-specimen,
x100); f E-12: t hin fibrous layered tissue. (f E, 12-wk-specimen, x100). M: Embedded material.
PP-1). t he material attached to the surface area of the flammatory cell infiltration in the tissue; thus, the
tisgranulation tissue was stained well by eosin, showing sue began to change to fibrous tissue.
necrotic changes. Just under the region, inflammatory
cell-rich granulation tissue was observed. t he enlarged Po l YEt HYl En E: PE
view showed there were some inflammatory cells and
a few fibroblasts in the surface eosin-stained region. In 1-week specimens, proliferation of scattered
granua fter 12 weeks, a thin fibrous tissue capsule tissue lation tissue was observed around the embedded
materwas formed (f ig.1, PP-12). t here was almost no in- ial (f ig. 1, PE-1). In the scattered granulation tissues,2) Kawakami T_Umbruchvorlage 03.06.11 17:13 Seite 251
June 21, 2011 Eu Ro PEa n Jo u Rn a l o f MEd ICa l RESEa RCH 251
there was some lymphocyte-rich inflammatory cell infil- medical use as biomaterials within the body. a s our
tration as well as capillaries showing hyperemia. t he study complied with the ISo ’s biological Evaluation
en larged view showed that there were some eosin uni- of Medical d evices Standard Part 12, we have
approformly-stained region, which suggested necrotic change. priately evaluated the histopathological safety of using
In 12-week specimen observations, the inflammato- PP, PE and f E subcutaneously.
ry cell infiltration had almost disappeared in the
prolifAcknowledgments: t he authors thank Professor d M Carlsonerated granulation tissues. t he granulation tissues
of Matsumoto d ental u niversity, for his critical reading ofchanged to fibrous tissues (f ig. 1, PE-12). a ttached
the manuscript.the surface of the determination edge of the
embedded material was a thin fibrous tissue layer, which
covered the scattered connective tissues. Some capillaries
REf EREn CESshowing hyperemia were observed in the tissues.
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implantation. bo n EZone 2006; 5(1): 50-52.Po l Yt Et Ra f l u o Ro Et HYl En E ：f E
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biological Evaluation of Medical d evices –Part 1: Evalua-In histopathological observations of 1-week
specition and testing, ISo 10993-1:2003 (E). g eneva, Switzer-mens, we note that a thin layered fibrous capsule tissue
land. 2003.formed around the embedded material (f ig. 1, f E-1).
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